Muscle atrophy refers to a state that muscle mass decreases due to reduction of muscle fiber number and reduction of muscle fiber volume, and is usually accompanied by decreased muscle force. Although appropriate exercise is effective for prophylaxis or improvement of muscle atrophy, recovery by exercise is difficult for sick persons and old people. Therefore, development of a drug or food effective for suppression or improvement of muscle atrophy is expected.
As techniques for inhibiting muscle atrophy using ingredients contained in plants, there are known muscle atrophy inhibitors containing Araliaceae ginseng radix (Patent document 1), α-glucosylated hesperidin (Patent document 2), or stigmasterol (Patent document 3) as an active ingredient, and an inhibitor of muscle fiber type shift containing a fruit-derived polyphenol (Patent document 4) as an active ingredient.
Further, as techniques for improving muscle function or suppressing reduction of muscle function, there are known a muscle function reduction inhibitor containing catechins as an active ingredient (Patent document 5), a endurance improver containing resveratrol and/or grape leaf extract as an active ingredient (Patent document 6), an anti-amyotrophic lateral sclerosis (ALS) agent containing rosmarinic acid or carnosic acid as an active ingredient (Patent document 7), and an anti-ALS agent containing a rosemary extract or sage extract as an active ingredient (Patent document 8).
As a plant-derived health food raw material, extract of Citrus depressa attracts attention. Various efficacies of polymethoxyflavonoids such as nobiletin and tangeretin contained in extract of Citrus depressa have been found to date. For example, it is reported that nobiletin has a neurite outgrowth action (Patent document 9), anti-hypertension and anti-cancer actions (Patent document 10), heart disease preventing and treating actions (Patent document 11), antiulcer action (Patent document 12), and so forth. Further, it has been reported that polymethoxyflavonoids such as tangeretin and nobiletin have a neovascularization suppressing action (Patent document 13). Furthermore, it is known that flavonoids contained in Citrus species such as Citrus depressa have a blood pressure elevation suppressing action (Patent document 14).
Further, the aforementioned inhibitor of muscle fiber type shift (Patent document 4) uses a polyphenol such as, specifically, procyanidin contained in fruits of Rosaceae plants such as apple, as an active ingredient.
However, such flavonoids as mentioned above are scarcely contained in fruit juice, but are mostly contained in pericarps. Therefore, only by squeezing fruits, these flavonoids are obtained only at a low content.
Polymethoxyflavonoids constitute one class of flavonoid, have a special structure in which a plurality of phenolic hydroxyl groups are methylated, and are mainly contained in Citrus species. It has also been reported that polymethoxyflavonoids such as nobiletin or tangeretin are metabolized in the liver after intake, and the generated metabolites enhance anti-inflammatory action. For example, methoxy groups of nobiletin are converted into hydroxyl groups by metabolism in the liver of rat, and nobiletin derivatives having 4′-OH, 7-OH, 6-OH, 3′,4′-diOH, 6,7-diOH or the like are generated as metabolites. Further, it has been reported that, from tangeretin, tangeretin derivatives having 4′-OH, 3′,4′-diOH, 7,4′-diOH, 6,7-diOH or the like are generated as metabolites (Non-patent document 1).
Although several plant-derived ingredients having a muscle atrophy inhibition action are known as described above, it is not known that extract of Citrus depressa or a polymethoxyflavonoid such as nobiletin and tangeretin has a muscle atrophy inhibition action.
As a method for preparing a muscle atrophy model for evaluating food materials, a method using a glucocorticoid, and a method using hindlimb immobilization or unloading are known. There have been reported that effect of a branched chain amino acid on cross-sectional areas of muscle fibers etc. (Non-patent document 2), and effects of creatine (Non-patent document 3) and vitamin E (Non-patent document 4) on muscle weight were evaluated by using a muscle atrophy model derived with a glucocorticoid. Further, there have also been reported that effects of resveratrol (Non-patent document 5) and fish oil (Non-patent document 6) on muscle weight were evaluated by using a muscle atrophy model prepared by using hindlimb immobilization or unloading.
However, there is no report concerning evaluation of muscle atrophy inhibition action of extract of Citrus depressa or ingredients thereof with these models or others.